title: Role of HO-1 in the arsenite-induced neurotoxicity in primary cultured cortical neurons.
abstract: In the present study, the role of heme oxygenase (HO)-1 in sodium arsenite (arsenite)-induced neurotoxicity was investigated using primary cultured cortical neurons. Incubation with arsenite was found to cause cell death of primary cultured cortical neurons in concentration- and time-dependent manners. Furthermore, arsenite induced caspase 3 activation and decreased procaspase 12 levels, indicating that apoptosis is involved in the arsenite-induced neurotoxicity. The oxidative mechanism underlying arsenite-induced neurotoxicity was investigated. Western blot assay showed that arsenite significantly increased HO-1 levels, a redox-regulated protein. Co-incubation with glutathione (10 mM) attenuated arsenite-induced HO-1 elevation and caspase 3 activation, suggesting that oxidative stress is involved in the arsenite-induced neurotoxicity. The neurotoxic effects of inorganic arsenics were compared; arsenite was more potent than arsenate in inducing HO-1 expression and caspase 3 activation. Moreover, the cell viabilities of arsenite and arsenate were 60 ± 2 and 99 ± 2 % of control, respectively. HO-1 siRNA transfection was employed to prevent arsenite-induced HO-1 elevation. At the same time, arsenite-induced caspase 3 activation and neuronal death were attenuated in the HO-1 siRNA-transfected cells. Taken together, HO-1 appears to be neuroprotective in the arsenite-induced neurotoxicity in primary cultured cortical neurons. In addition to antioxidants, HO-1 elevation may be a neuroprotective strategy for arsenite-induced neurotoxicity.
authors.affiliation: Institute of Physiology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Y C
authors.initials: YC
authors.lastname: Teng
authors.forename: Y I
authors.initials: YI
authors.lastname: Tai
authors.forename: Y H
authors.initials: YH
authors.lastname: Lee
authors.forename: A M Y
authors.initials: AM
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000633:toxicity*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D005978:Glutathione / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D018053:Arsenites; D009498:Neurotoxins; D034741:RNA, Small Interfering; D051547:Heme Oxygenase-1; D005978:Glutathione; C015001:arsenite